Methods and apparatus for testing disruption of a vagal nerve

ABSTRACT

Method and apparatus for disrupting a gastric vagal nerve in the gastroesophageal region and testing the function and disruption of the vagal nerve. In one example embodiment, a treatment device applies ultrasound at a high energy level, such as high intensity focused ultrasound, to a vagal nerve to disrupt it and then ultrasound at a lower energy level to another portion of the vagal nerve, preferably further from the stomach, so as to stimulate the vagal nerve. Alternative ways to test the function or disruption of the vagal nerve involve using PCP-GABA, a pancreatic polypeptide, pressure changes inside the stomach, the gastric mucusol pH, a dye agent in the stomach, and other tests.

CROSS REFERENCE TO RELATED PATENT APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 10/389,236, titled “Methods and Apparatus for Treatment ofObesity,” filed Mar. 14, 2003.

FIELD OF THE INVENTION

The field of the present invention is methods and devices for treatingobesity, and more particularly, methods and devices for disrupting avagal nerve and testing the disruption of the function of the vagalnerve.

BACKGROUND OF THE INVENTION

Obesity has become an ever-increasing health problem. While suchvoluntary weight reduction programs as dieting and exercise have beenhelpful for some, many obese persons have required surgery to addresstheir obesity problem. Two such surgical procedures are vertical bandedgastroplasty (VBG) and the Roux-en-Y gastric bypass procedure. Both suchprocedures are now well known, but they are invasive in nature andinvolve reducing the size of the stomach. The parent patent applicationdescribes novel methods and devices for treating obesity by disruptingthe vagal nerve. Because an incompletely disrupted vagal nerve stillcontrol appetite and certain stomach functions, there is a need to testthe function and disruption of the vagal nerve.

SUMMARY OF THE INVENTION

The preferred embodiment of the present invention uses an elongatedevice that outputs energy to disrupt the function of the vagal nervefrom within the esophagus and then applies at least one of a variety oftests to determine whether the vagal nerve has been disrupted. Bymonitoring the stomach, such as monitoring for changes in pressure inthe stomach or the gastric mucusol pH, one may determine whether thevagal nerve has been disrupted. Alternative methods for testing thecompleteness of the vagotomy include using a pancreatic polypeptide suchas PCP-GABA, a dye agent such as Congo Red, the Burge test, the Grassitest, augmented histamine test, a neurotransmitter amino acid, and othertests described later in this application. An example embodiment uses atreatment device capable of outputting two different energy levels. Thetreatment device preferably outputs at a high energy level sufficient todisrupt a vagal nerve. Then the physician moves the treatment device toanother location, preferably at a location further from the stomach, andapplies a low energy level sufficient to stimulate the vagal nervewithout disrupting the nerve. An alternative to using the treatmentdevice to output a low energy level, other devices may apply anelectrical voltage to stimulate the vagal nerve.

Other systems, methods, features and advantages of the invention will beor will become apparent to one with skill in the art upon examination ofthe following figures and detailed description. It is intended that allsuch additional systems, methods, features and advantages be includedwithin this description, be within the scope of the invention, and beprotected by the accompanying claims. It is also intended that theinvention is not limited to require the details of the exampleembodiments.

DESCRIPTION OF THE DRAWINGS

The details of the invention, including fabrication, structure andoperation, may be gleaned in part by study of the accompanying figures,in which like reference numerals refer to like segments. The figures arenot to scale and the size of the features in relation to each other isnot intended to limit the invention in any way.

FIG. 1 is a diagrammatic illustration of the general anatomy of thestomach and esophagus.

FIG. 2 illustrates positioning of an ablation device using a singleballoon installed above the diaphragm.

FIG. 3 illustrates positioning the ablation device using a balloon whichis inflated in the stomach.

FIG. 4 illustrates a positioning device using radially extending feet.

FIG. 5 illustrates a positioning device using a bite block.

FIG. 6 is a diagrammatic illustrate of the use of needles or electrodesto detect and ablate around the circumference of the outer surface ofthe esophagus in a manner designed to interrupt all vagal nervebranches.

FIG. 7 is an illustration of an ablating device which ablates a sectorof the circumference of the outer wall of the esophagus.

FIG. 8 shows ablating at multiple levels.

FIG. 9 illustrates an ablation ring which can be adjusted to ablate atdifferent angles relative to the access of the esophagus.

FIG. 10 illustrates the use of still another ablation device to locateand interrupt the vagal nerve.

FIG. 11 illustrates an endoluminal burge test which can be used todetermine the extent of ablation accomplished.

FIG. 12 shows an ultrasound ablating device which may be used accordingto the present invention.

FIG. 13A illustrates an ultrasound device installed in the esophagus.

FIG. 13B illustrates the stomach and esophagus with an elongate devicewith a D-shaped distal tip.

FIG. 13C illustrates a cross section of the esophagus of FIG. 13B toshow the D shaped distal tip inside the esophagus.

FIG. 14 illustrates an ablation device installed in the esophagus in amanner which shows the esophagus held in its naturally relaxedconfiguration by a transducer device.

FIGS. 15 and 16 illustrate an alternative to the device shown in FIG.14.

FIG. 17A illustrates a perspective view of a preferred embodiment of thepresent invention when the ultrasound transducer platform is in a fullylowered position.

FIG. 17B illustrates a perspective view of a preferred embodiment of thepresent invention when the ultrasound transducer platform is in a fullyraised position.

FIG. 18 illustrates a perspective view of a preferred embodiment of thetransducer platform.

FIG. 19 illustrates a perspective view of a preferred embodiment of aposition actuator.

FIG. 20 illustrates an example of the focal point and distribution ofenergy emitted from the ultrasound transducer.

DETAILED DESCRIPTION OF THE INVENTION

Before turning to the manner in which the present invention functions,it is believed that it will be useful to briefly review the anatomy ofthe stomach and the esophagus. The esophagus is a muscular tube thatcarries food from the throat to the stomach and which passes through thediaphragm. The top end of the esophagus is the narrowest part of theentire digestive system and is encircled by a sphincter (circularmuscle) that is normally closed but can open to allow the passage offood. There is a similar sphincter at the point where the esophagusenters the stomach. The walls of the esophagus consist of strong musclefibers arranged in bundles, some circular and others longitudinal. Theinner lining of the esophagus consists of smooth squamous epithelium(flattened cells).

As shown in FIG. 1, the esophagus 1 extends through the diaphragm 2 intothe stomach 3. Vagal nerve branches extend from the stomach along theouter wall of the esophagus to the brain. At the lower end of theesophagus, the juncture of the esophageal and gastric mucosa forms azig-zag line 4, usually referred to as the Z-line. In the area extendingfrom the diaphragm to a point below the Z-line, there is a subhiatal fatring which surrounds the outer wall of the esophagus. The vagal nervebranches run between the outer wall of the esophagus and the hiatal fatring in this area. This anatomy is well understood by those skilled inthe art and a more detailed description can readily be found in astandard work such as Gray's Anatomy.

It appears that a hunger signal is expressed by ghrelin, a peptideprimarily produced in the stomach, and transmitted to the brain throughthe vagal nerve. The literature e.g., “The Role of the Gastric AfferentVagal Nerve in Ghrelin-Induced Feeding and Growth Hormone Secretion inRats,” Gastroenterology 2002:123:1120-1128 (October 2002) by Yukari Dateet al. and “Gastroplasty for Obesity: Long-term Weight Loss Improved byVagotomy,” World Journal of Surgery, Vol. 17, No. 1, January/February1993, by Kral et al., supports this theory. The Date et al. articleconcluded that blockade of the gastric vagal afferent abolishedghrelin-induced feeding in rats and the Kral et al. article concludedthat vagotomy combined with gastroplasty was more effective incontrolling weight loss than gastroplasty alone. These articles areincorporated by reference herein.

The parent patent application treats obesity by interrupting the vagalnerve, preferably in the region of the esophagus, by minimally ornoninvasive means. The vagal nerve branches may be disrupted in atransesophageal manner by using various types of energy including radiofrequency (RF) energy, high intensity ultrasound, high intensity focusedultrasound, and other types of energy as described in more detail below.The energy source may be installed in the esophagus through the throat,but nasogastric access through the nose and extracorporeal applicationare also contemplated. The energy may be delivered to the vagal nervethrough the esophagus wall, e.g., when ultrasound is used, or by causingan energy delivery device, e.g., an electrode to be passed through thewall of the esophagus.

Typically, there are two main branches, or trunks, of the vagal nervewhich are located approximately 180° from each other on the outer wallof the esophagus. Depending on patient needs, it may be sufficient tointerrupt only a portion of the fibers in the nerve. In this regard, itis to be noted that, in general, myelinated vagal nerve fibers, i.e.,fibers that have an outer coating, are efferent. In contrast, afferentvagal nerves are unmyelinated and have no outer covering. For somepatients, it may be sufficient to interrupt the function of only theafferent vagal fibers.

Still other energy sources can be used to interrupt the function of thevagal nerves including thermal, microwave, laser and cryogenic energy.Alternatively, the vagal nerve function can be interrupted bytransesophageal delivery of a neurotoxin such as capsaicin, atropine, orbotulinum toxin. Still further, mechanical means can be used to crushthe vagal nerve, e.g., with a clip or pincer, or the vagal nerve can becut transesophageally with an appropriate cutting instrument. In apreferred embodiment of the present invention, the vagal nerve will beinterrupted in the vicinity of the zig-zag line, also known as theZ-line, which is generally located in the lower esophagus between thecardiac notch of the stomach and the diaphragm. However, the inventioncan be used to disrupt the vagal nerve at other locations, such as atthe diaphragm.

The objective is, of course, weight loss by the patient as a result ofinterruption of efferent gastric and afferent hormonal signalstransmitted through the vagal nerve branches. Thus, the success of theprocedure described herein will, to some extent, be patient-dependentand, in some patients, it may be necessary to interrupt both theafferent and efferent vagal fibers, both of which may be found in theposterior and anterior branches.

FIG. 2 illustrates in a diagrammatic manner an ablation device 5 whichis held in place by balloon 6 which is inflated inside the upper portionof the esophagus. FIG. 3 illustrates positioning the ablation device 5with balloon 7 which is inflated inside stomach 3. FIG. 4 illustratespositioning the ablation device 5 with feet 6 which pass through theesophagus folded against the ablation device 5 and then are extendedinside stomach 3. FIG. 5 illustrates the use of a bite block 7 toposition the ablation device 5 in stomach 3. FIG. 6 is a diagrammatictransverse cross section of the esophagus showing, in diagrammatic form,the esophagus wall 1, vagal nerve branches 8, a detection/ablationdevice 9 having needle probes 10. As shown, the needle probes 10 extendthrough the wall of the esophagus and can be used both to locate thevagus nerve and to ablate it. For detection purposes, the needle probes10 are connected to an exterior control unit that detects and displaysnerve activity in a manner well known to those skilled in the art. Oncea vagal nerve is detected by a needle probe by sensing the activity ofthe nerve upon contact, the adjacent needle probes are energized and actin the manner of bipolar cautery probes which ablate the nerve and anyother tissue between the needle probes. Preferably, the needle probesare designed in such a manner that they are held within the body of theablation device until the device reaches its desired location. Theneedle probes can then be extended to penetrate the wall of theesophagus once the device has been positioned. Preferably, the needleprobes are designed so that the electric current flows only at theirtips so that the depth of the cautery can be focused to minimize damageto the esophagus. Cosman U.S. Pat. No. 4,565,200, Rydell U.S. Pat. No.5,007,908, Edwards U.S. Pat. No. 5,370,675 and Edwards U.S. Pat. No.6,129,726, each of which is incorporated by reference herein, disclosevarious types of electrode needle probe devices which can be used todeliver RF energy to tissue located within the body. Each of thesepatents discloses a device in which the needle probes are containedwithin the device until it has reached its desired location, at whichtime the needle probes are deployed to contact the tissue to whichenergy is to be delivered.

In the present invention, the needle probes can irradiate around thecomplete circumference of the device as shown in FIG. 6 or from only aportion of the device as shown in FIG. 7. If the latter, the device canbe rotated sequentially to ensure complete coverage. As further shown inFIG. 7, when the needle probes 13 radiate from only a portion of thecircumference of the device 12, a back balloon 11 can be used toposition the device 12 in the desired location.

FIG. 10 illustrates an alternative sector-specific ablation device inwhich needle probes 13 are activated by device 12 to locate and ablatethe vagal nerve in the manner described above. If a patient can obtainthe desired benefit of obesity reduction by ablating the two main vagusbranches 8, the procedure is simplified and the amount of ablationnecessary is reduced. On the other hand, as shown in FIG. 8, if multipleablation levels 14 are found to be necessary to provide the desiredbenefit to the patients, more than one ablation can be performed.

If the patient's anatomy makes it desirable, an ablation device 5 can beprovided with an energy delivery component 15 which is adjustable suchthat energy can be delivered perpendicularly to the probe or at an angleto the probe.

When a needle probe is used to deliver energy according to the presentinvention, the device can be provided with temperature sensors such asthermocouples which are disposed in the distal region of the needleprobes. The needle probes can be formed of a variety of materialsincluding nickel-titanium alloy. The needle probes can assume a linearor curved shape when deployed. The device may also be provided withmeans for cooling the treatment site with a suitable fluid such aswater, air, or other liquid or gas, to control the temperature at thetreatment site. Thus, the temperature sensor can either cause a coolingmedium to be provided or shut off the delivery of energy through one ormore needle probes.

In a preferred embodiment of the present invention, high intensityfocused ultrasound (HIFU) is used to ablate the vagal nerve branches.The HIFU energy can be transmitted transesophageally to ablate the vagalnerves on the outer wall of the esophagus.

FIG. 12 illustrates in a diagrammatic form an ultrasound device whichcan be used according to the present invention. As shown, the devicecomprises an elongated member 16 which has an ultrasound transducer 17mounted on its distal region. The elongated member is positioned in ahousing 18 which is provided with an inflatable balloon 19. This devicemay be installed by passing it through the throat and down the esophagusuntil it reaches its desired location with the balloon 19 deflated.Xray, magnetic resonance imaging, or other known imaging techniques maybe used to ascertain the positioning of the treatment device 50, or anyother device described herein, in the gastroesophageal region, includingaxially down the esophagus and rotationally toward the anterior vagusnerve trunk. After rotating the treatment device 50, for example by 180degrees to target the posterior vagus nerve trunk, the new position ofthe device 50 may be confirmed by xray, magnetic resonance imaging, orother known imaging techniques. The balloon 19 can then be inflated toposition the device and the ultrasound transducer can be activated totransmit energy radially outwardly. Alternatively, a vacuum device canbe used to position the housing.

As shown in FIGS. 17A and 17B, a treatment device 50 is movable alongtwo or three axes. In particular, the treatment device 50 may be movedlongitudinally along the axis of the esophagus to a further or closerdistal position, transversely along the radius of the esophagus, androtationally about the axis of the esophagus. These three degrees offreedom are relative to the esophagus. The treatment device 50 has anultrasound device 54 and preferably treats obesity by disrupting thevagal nerve adjacent the esophagus. In this example embodiment, amovable platform 52 carries a high focus ultrasound (HIFU) transducerdevice 54. The transducer 54 may be have an air-backing 55, or othertypes of known transducer backing materials. FIG. 17A illustrates aperspective view of the preferred embodiment when the platform 52 is ina fully lowered position, while FIG. 17B illustrates a perspective viewwhen the platform 52 is in a fully raised position. Of course, theultrasound transducer 54 may move anywhere between the fully raisedposition and the fully lowered position. Thus, the platform 52 may movethe ultrasound transducer 54 closer to or farther from a treatmentwindow 72 so as to control the focal point of the energy output from theultrasound transducer 54. As the ultrasound transducer 54 moves fartherfrom the treatment window 72, the focal point of the energy from theultrasound transducer 54 moves closer to the wall of the esophagus. FIG.20 illustrates an example of the focal point 90 and distribution 92 ofenergy emitted from the ultrasound transducer. Thus, the focal point 90is adjustable. Preferably, the focal point 90 is directed at the site ofa vagal nerve and away from the esophagus wall.

FIG. 18 illustrates a perspective view of an example embodiment of thetransducer platform 52. The platform 52 preferably carries a highintensity focused ultrasound transducer 54 and an ultrasound imagingtransducer 56. The ultrasound imaging transducer 56 performs diagnosticimaging for monitoring the formation of lesions in the esophagus and fordefining the outside of the esophagus for the purpose of locating thevagal nerve. The ultrasound imaging transducer 56 can be any known typeof imaging transducer such as those that are mechanically based (e.g.,rotating and pivoting transducers) or piezo electrically based phasedarrays, which have, for example, 128 imaging transducers.

The platform 52 also may include circulation channels 58 for allowingfluid, such as saline, to flow into the device and around the ultrasoundtransducer 54 so as to improve the acoustic characteristics of theultrasound transducer 54 or to cool the transducer 54. Even though thetransducer 54 is illustrated as having a curved surface, the ultrasoundtransducer 54 may have any geometry, size, shape and curvature asappropriate.

The platform 52 has one or more guide rails or guide bosses 60, whichcouple to guide slots 62 of the position actuator 64 shown in FIG. 19,which illustrates a perspective view of an example embodiment of theposition actuator 64. Because the guide bosses 60 ride in upward slantedguide slots 62, movement of the distal end 88 of the position actuator64 toward the platform 52 causes the platform 52 to rise toward thetreatment window 72. The upper limit stops 70 on the platform 52 createan upper limit of motion for the platform 52. Of course, variations arealso contemplated. For example, the guide slots 62 can be in a fallingconfiguration so that movement of the distal end 88 of the positionactuator 64 toward the platform 52 causes the platform 52 to retreatfrom the treatment window 72. As another example, guide bosses 60 andguide slots 62 may be replaced by any other known mechanism, such asgears, levers or a set of guide rails, to translate the platform 52toward and away from the treatment window. The guide bosses 60 may be ontwo or more sides of the platform 52, which would require guide slots 62on two or more corresponding sides of the position actuator 64. Theupper limit stops 70 could hang from the inner surface of the wallhaving the treatment window 72 instead of being on the platform 52.

As shown in FIG. 19, the position actuator 64 has an elongate member 66so the physician can push the actuator 64 distally or pull the actuator64 proximally. A forward stop 74 defines the furthest distal positionthat the position actuator 64 may be moved.

Turning to FIG. 17A, the platform 52 is shown in its fully loweredposition. As such, the forward stop 74 of the position actuator 64 isnot engaged with corresponding stop 76 in treatment device 50. FIG. 17Aalso illustrates a nerve mapping device 80, which is preferably a 10×10constant current impedance grid for nerve mapping. A thermocouple 71 tomonitor the mucosal layer may also be provided on the outer surface ofthe treatment device 50.

An inflow channel 84 and outflow channel 86 may be provided so thatfluids, such as saline, may flow through the treatment device 50.Additionally, optional micro holes 87 may be provided in the wall of thetreatment device 50 to facilitate the flow of fluids into and out of thedevice 50.

Comparing FIG. 17A to FIG. 17B, one will see that the position actuator64 in FIG. 17B is fully inserted so that the forward stop 74 has engagedcorresponding stop 76, and the platform 52 is fully raised. Therefore,in this example preferred embodiment, moving the position actuator 64distally relative to the treatment device 50 causes the platform 52 tomove toward the treatment window 72. Conversely, in this examplepreferred embodiment, moving the position actuator 64 proximallyrelative to the treatment device 50 causes the platform 52 to move awayfrom the treatment window 72. Thus, the treatment device 50 permits theposition of the ultrasound transducer 54 relative to the treatmentwindow 72, and thus, the esophageal wall, to be adjusted. The adjustablepositioning of the ultrasound transducer 54 along this radial axispermits control over the focusing of the energy emitted from theultrasound transducer 54 onto the vagal nerve in the region of theesophagus while avoiding injury to the esophageal wall.

Besides moving transversely along the radial axis of the esophagus, theplatform 52 and ultrasound transducer 54 may be moved along thelongitudinal axis of the esophagus to a further or closer distalposition. Because the ultrasound transducer 54 can be movedlongitudinally, e.g., closer or further from the stomach, the treatmentdevice 50 can be more accurately positioned to ablate or otherwisedisrupt the vagal nerve. Moreover, the treatment device 50 may be usedto deliver ablating energy to one vagal nerve branch in atransesophageal manner, and then moved to another vagal nerve branch forfurther disruption of the vagal nerve system or for testing thecompleteness of the prior disruption of the vagal nerve.

A preferred method of disrupting the vagal nerves is as follows: First,a treatment device 50, or any other device described herein, ispositioned at the appropriate location in the esophagus, preferably withthe assistance of xray, magnetic resonance imaging, or other knownimaging techniques. Such imaging techniques may be used to properlyposition the treatment device axially down the esophagus androtationally toward the anterior vagus nerve trunk. Then the inneresophagus is cooled and the ablation depth is adjusted with an imagingcrystal along a radial line of the esophagus. High level energy isemitted from the treatment device, such as from a HIFU transducer, toablate and disrupt the anterior vagal nerve branch. Then the treatmentdevice is rotated by 180 degrees to target the posterior vagus nervetrunk, where the new position of the treatment device may be confirmedby xray, magnetic resonance imaging, or other known imaging techniques.Once the new position of the treatment device is confirmed as beingappropriate, the ablation depth is adjusted with an imaging crystalalong a radial line of the esophagus and high level energy is emittedfrom the treatment device to ablate and disrupt the posterior vagalnerve branch.

FIG. 13A is a diagrammatic illustration of an ultrasound transducerinstalled in the esophagus. As shown in this figure, the transducerdevice 16 is installed in the esophagus 1 in the region of the Z-line 4.The subhiatal fat ring 20 is also shown. When the transducer 17 isactivated, ablating energy will be radiated through the wall of theesophagus to ablate the vagal nerve branches 21 which are also showndiagrammatically.

Although the esophagus is generally illustrated anatomically as agenerally cylindrical tube, in its relaxed condition it assumes a moreelliptical configuration which can be characterized as floppy. In otherwords, somewhat like a sock before it is put upon a foot, it does notassume a generally circular configuration unless it contains food orother object, but otherwise has a configuration in which the opposingwalls of the esophagus are closer together than they would be when in acircular configuration. For example, FIG. 13B illustrates the stomach 3and esophagus 1 when an elongate device 28 having a D-shaped distal tip30 is in place in the esophagus 1. The elongate device 28 is preferablythin, flexible and torqueable. The “D” shape of the distal tip 30 causesthe esophagheal wall to take on a D shape, with a flat portion 31, asfurther illustrated in the cross section illustration of FIG. 13C. FIG.13C illustrates a cross section of the esophagus 1 when the D-shapeddistal tip 30 is in place. A HIFU transducer 32 is preferably inside theD-shaped distal tip. By positioning the HIFU transducer 32, which ispreferably directed to focus its energy at the flat portion 31 of the D,there is an ablation zone 36 that encompasses the anterior vagal nerve34. By rotating the D-shaped distal tip 30, the ablation zone caninclude the posterior vagal nerve 38 or a vagal nerve branch. Thus, whenthe treatment device 50 is inserted into the esophagus, a cross sectionof the esophagus would preferably be D-shaped, where the focal point ofthe energy would be directed in the direction of the flat portion of the“D.”

In FIG. 14, esophagus 1 with vagal nerve branches 8 on its outer wall isprovided with a transducer 22 which has radially extending struts 23.Each of these struts 23 has a rounded portion 24 at its distal end. Thestruts 23 and 24 serve to hold the esophagus in its relaxed generallyelliptical shape and to hold the transducer 22 in the desired locationas well. In an alternative embodiment illustrated in FIGS. 15 and 16,balloons 25 mounted on the side of the transducer-containing device 26are implemented to hold the esophagus in a more ellipitical shape. Whenthese types of devices are used, the transducer device 22 or 26 could beconstructed to direct ultrasound energy towards the vagal nerve branches8 in one direction or in two directions. FIG. 15 shows the balloons 25in the deflated state and FIG. 16 shows the balloons in the inflatedstate.

Ultrasound heating technology, including high-intensity ultrasound andHIFU are well understood. For example, Chapter 12, entitled “Ultrasoundheating technology,” of “Thermo-radiotherapy and Thermo-chemotherapy,”vol. 1, edited by Seegenschmiedt, Fessenden and Vernon, contains athorough explanation of the use of ultrasound in thermal therapy. Thischapter is incorporated by reference herein.

Having explained various methods and apparatuses for treating obesity bydisrupting the vagal nerve transesophageally, the present invention is,in general, directed to testing whether the vagal nerve, preferably inthe region of the esophagus, has been disrupted and testing the amountof disruption to the vagal nerve.

One example embodiment of the present invention is to use the treatmentdevice 50 described above, where the treatment device 50 is adapted todeliver energy at two or more levels: a high energy level sufficient todisrupt a gastric vagal nerve and a low energy level sufficient tostimulate a gastric vagal nerve without disrupting the nerve. Theultrasound energy levels may be described by itsspatial-peak-temporal-average intensity (Ispta), which is measured inmW/cm² or W/cm². For example, a low energy level exposure includes therange of about 50 mW/cm² to 50 W/cm², and preferably is between about500 mW/cm² to 5 W/cm². A high energy level exposure includes the rangeof about 50 to 5000 W/cm², and preferably is between about 300 to 3000W/cm². The ultrasound exposure time may range from a few seconds (forexample, one to 30 seconds) to minutes (for example, up to 60 minutesand preferably not to exceed five minutes). The shorter the exposuretime, the higher the Ispta intensity needs to be for the desiredtreatment effect. To stimulate the vagal nerve, one may alternativelytry a high energy level exposure, but for a shorter exposure time. Theultrasound frequency range preferably is about two to ten MHz, and morepreferably is about three to eight MHz.

A preferred example method of the present invention is, generally, todisrupt the gastric vagal nerve transesophageally and to test whetherthe vagal nerve has been disrupted. Optionally, the method woulddetermine the amount of disruption. One example method involves thesteps of introducing the treatment device 50 into the esophagus,positioning its source of energy, e.g., an ultrasound transducer 54, ata location below the diaphragm, delivering energy from the ultrasoundtransducer 54 at a high energy level, which means an energy levelsufficient to disrupt a vagal nerve located outside the esophagus wall,and then testing the disruption of the vagal nerve. There are numerousways to test the disruption of the vagal nerve, all of which arecontemplated for use with the present invention.

For example, the physician may retract the treatment device 50 away fromthe location at which the high level energy was directed and preferablyabout one centimeter to an inch further away from the stomach. Then thetreatment device 50 is used to deliver a lower level energy from theultrasound transducer 54 to another portion of the vagal nerve. By usinga lower level energy, meaning an energy level sufficient to stimulatethe vagal nerve without disrupting the nerve, one can stimulate thevagal nerve at a location not disrupted by the high level energy so thatone can test whether the vagal nerve was disrupted and how much it hasbeen disrupted.

To test whether the vagal nerve was disrupted and potentially how muchit has been disrupted, several different methods may be used. Forinstance, one may use a pressure transducer in the stomach to measurethe pressure in the stomach before and after delivering the lower levelenergy to the vagal nerve, and then compare the pressures to see if thepressure changed substantially in response to stimulation of the vagalnerve. If the pressure does not change substantially, it is presumedthat the vagal nerve has been disrupted completely or substantiallycompletely. Greater pressure changes in the stomach indicate that thedegree of disruption of the vagal nerve may be lesser.

As another example, one may apply a dye agent, such as Congo Red, intothe stomach after delivery of the lower level energy to stimulate thevagal nerve and measure the amount of time required for the dye tochange from a red color to a black color. If the vagotomy was complete,Congo Red would require approximately 10-20 minutes to change to a blackcolor. If the vagotomy was significantly incomplete, Congo Red wouldchange much more rapidly to a black color.

As yet another example, one may use a pressure transducer in the stomachto measure the pressure in the stomach before and after stimulating thevagal nerve. The pressure transducer allows one to determine the amountof change in pressure, if any, as a result of the stimulation of thevagal nerve. One may conclude that the vagal nerve was completelydisrupted if the pressure in the stomach does not change in response tostimulus of the vagal nerves or the vagal centers of the brain. On theother hand, greater pressure changes may indicate less disruption of thevagal nerve. Instead of analyzing the change in pressure, one may beable to determine that the vagal nerve has not been disrupted if thepressure in the stomach after vagal nerve stimulation falls within thenormal range of pressures for intact vagal nerves. Analyzing the changein pressure is preferred over merely measuring the pressure.

Still another example of a method for determining whether the vagalnerve was disrupted and the amount of disruption includes measuring agastric mucosal pH of the stomach after stimulating the vagal nerve orthe vagal centers in the brain. Any known device and method formeasuring the gastric mucosal pH of the stomach may be used, such as anintraluminal combination electrode. If the gastric mucosal pH is lessacidic than normal, e.g., pH of 6, one may conclude that the vagal nervehas been disrupted. Greater disruption to the vagal nerve may result ina smaller acidic response in the stomach mucosal.

As still another example, one may measure the pancreatic polypeptideresponse to sham feeding and/or phamacological stimulation. SeeNagammapudur, S. et al., A Safe and Noninvasive Test for Vagal IntegrityRevisited, Arch. Surg., Vol. 137, August 2002, pp. 954-957, the entiretyof which is incorporated herein by reference. A rise of greater thanfifty percent in the pancreatic polypeptide level within thirty minutesof sham feeding is a strong indicator of vagal integrity. Pancreaticpolypeptide response is known to be biphasic, as an early responseoccurs ten to thirty minutes after vagal stimulation and a prolongedsecondary response occurs after thirty minutes to six hours.

As another example, the Burge test may be used. The Burge test uses anesophagus-encircling vagal stimulating electrode placed through an openprocedure and depends on a motility response. See Burge, H. et al.,“Method Of Testing For Complete Nerve Section During Vagotomy,” BritishMedical Journal, Mar. 15, 1958, pp. 615-618; Burge, H. et al., “TheTechnique Of Bilateral Selective Vagotomy With The ElectricalStimulation Test,” Brit. J. Surg., Vol. 56, No. 6, June 1969, pp.452-460, both articles of which are incorporated herein in theirentirety. The Burge test preferably empties the stomach, applies 10-50volts to the vagal nerves, and then measures the change in gastricpressure.

A Burge test modified to use a balloon or inflatable cuff, as proposedby T. P. J. Hennessy, may also be used. See Hennessy, T. P. J. et al.,“An improved preoperative test of vagal section, Annals of the RoyalCollege of Surgeons of England,” Vol. 61, 1979, pp. 474-476, whicharticle is incorporated herein by reference in its entirety. Themodified Burge test, also referred to as the strain gauge test, usescheaper equipment than the Burge test. An example of the Burge testfollows. The patient is given oral diazepam and then anaesthesized. Alarge bore gastric tube is inserted into the stomach with an inflatablecuff lying in the lower esophagus. A Whitney mercury-in-rubber straingauge is sutured to the anterior stomach wall and then connected via aParks plethysmograph to a pen recorder. One then occludes the distalstomach with a soft clamp, inflates the cuff, and introduces air intothe stomach. Semicircular electrodes are placed around the esophagus, orif open surgery is not contemplated, an electrical stimulus may beapplied to the vagal nerve from within the esophagus. For example, anelectrical stimulus of 45 volts at 90 c/s with a pulse width of 10 ms isapplied for 20 seconds using a square wave stimulator. If the vagalnerves are intact, the simulus causes the stomach to distend, which isshown as a deflection on the strain gauge. A strain response of lessthan that produced by the introduction of 40 ml of air may not besignificant. In other words, if the response is less than the deflectionproduced by the addition of 40 ml of air, the vagotomy is likelycomplete.

The Grassi test may be used and employs the potentiating interactionsbetween vagal tone and histamine. The pH of the gastric mucosa ischecked with a pH meter connected with a glass electrode that slidesover a large surface of the gastric mucosa and to a reference electrodeon the oral mucosa. By comparing the pH of the gastric mucosa before andafter a vagotomy, with cleansing of the mucosa before the vagotomy andinjection of an augmented dose of histamine (0.024 milligrams perkilogram of histamine bichloridrate) after the vagotomy, one maydetermine whether the pH after the vagotomy is greater than 5.5. SeeGrassi, G. et al., “Intraoperative Relation Of Gastic Secretion AcidityAnd Complete Vagotomy,” Surgery, Gynecology & Obstetrics, Vol. 134,January 1972, pp. 35-38, which is incorporated herein in its entirety.

Having discussed various alternative methods for testing thecompleteness of the vagotomy, there are alternative embodiments forstimulating the vagal nerve. One alternative to using the treatmentdevice 50 to output ultrasound energy at a low level to stimulate thevagal nerve is to use a known device that can apply an electricalstimulus to the vagal nerve. Such devices may include probes or needlescarrying an electrical voltage.

Instead of delivering a lower level energy to stimulate the vagal nerve,one may introduce to the patient a substance such as PCP-GABA thatstimulates gastric activity by acting on vagal centers in the brain.Then one would measure the gastric mucosal pH of the stomach afterdelivery of the drug or substance. If the gastric mucosal pH is lessacidic than normal, e.g., pH of 6, one may conclude that the vagal nervehas been disrupted. The less acidic the stomach mucosal, the moredisruption there is to the vagal nerve. PCP-GABA and its use tostimulate gastric acid secretion by acting on vagal centers in the brainis described in Goto, Y. et al., “A New Intraoperative Test forCompleteness of Vagotomy: The PCP-GABA(Beta-Parachiorophenol-Gamma-Aminobutyric Acid) Test,” The American J.of Surgery, Vol. 147, January 1984, pp. 159-163, which article isincorporated herein in its entirety. Alternatively, one may use apressure transducer in the stomach and analyze any pressure change inthe stomach, or any of the other methods for analyzing the disruption ofthe vagal nerve.

As another alternative to delivering a lower level energy to stimulatethe vagal nerve, one may apply an electrical stimulus to the vagal nerveto stimulate it. One may monitor the stomach for acid changes in themucosa, pressure changes in the stomach, or any of the other methods foranalyzing the disruption of the vagal nerve.

As yet additional alternatives to delivering a lower level energy tostimulate the vagal nerve, one may introduce to the patient other knownstimulants such as insulin, 2-deoxy-glucose, neurotransmitter aminoacid, and histamine. 2-deoxy-glucose, which displaces glucoseintracellularly, was proposed by Cole. See Cole, “An Intra-operativeTest for the Completeness of Vagotomy, Am. J. Surg., Vol. 123, 1972, pp.543-44, which is incorporated herein in its entirety.

The insulin test first described by Hollander is another test that maybe used. This test examines the gastric acid secretion normally evokedby insulin induced hypoglycemia when the vagal nerves are intact. Acomparison of the acid response to insulin before and after vagotomyreveals the effect of vagotomy on acid secretion. An increase in acidconcentration of at least twenty mEq. per liter above basal levelswithin two hours after giving insulin to the patient indicates anincomplete vagotomy. A rise of 10 mEq. per liter is consideredacceptable if the spontaneous gastric secretion is anacid. Patientshaving intact vagal nerves generally have a positive gastric acidresponse within forty-five minutes of insulin administration. See Bell,P. R. F., “The Long Term Effect Of Vagotomy On The Maximal Acid ResponseTo Histamine In Man,” Univ. Dept. of Surgery, Royal Infirmary,Sheffield, England, Vol. 46, No. 4, pp. 387-391, and Ross, B. et al.,The Insulin Test After Vagotomy, The Univ. Dept. of Surgery, the RoyalInfirmary, Sheffield, England, Vol. 46, No. 4, pp. 379-386, botharticles of which are incorporated herein by reference in theirentirety.

The augmented histamine test, as described by Bell and Kay, is anothertest that may be used. In doing this test, one introduces a Ncoplexgastric tube through the nose into the stomach and applies constant pumpsuction to empty the stomach. 100 milligrams of mepyramine maleate(Anthisan) is injected intramuscularly, and gastric secretions for thenext thirty minutes are collected and discarded. Histamine acidphosphate (0.04 mg. per kilogram of body weight) is injectedsubcutaneously and three specimens of gastric secretion obtained atfifteen minute intervals. The acid output is measured by titration of afive milliliter portion against 0.1N sodium bydroxide with the use of aTopfer indicator. The last two specimens are added to represent themaximal acid response. Complete vagotomy should cause an immediatereduction of over fifty percent in the maximal acid response tohistamine. See Bell, P. R. F., “The Long Term Effect Of Vagotomy On TheMaximal Acid Response To Histamine In Man,” Univ. Dept. of Surgery,Royal Infirmary, Sheffield, England, Vol. 46, No. 4, pp. 387-391, whichis incorporated herein by reference in its entirety. This reduction ofmore than fifty percent is maintained for at least three years inpatients having a complete vagotomy.

In the foregoing specification, the invention has been described withreference to specific embodiments thereof. It will, however, be evidentthat various modifications and changes may be made thereto withoutdeparting from the broader spirit and scope of the invention. Forexample, each feature of one embodiment or method can be mixed andmatched with other features shown in other embodiments and methods. Asanother example, the order of steps of method embodiments may bechanged. Features and processes known to those of ordinary skill maysimilarly be incorporated as desired. Additionally and obviously,features may be added or subtracted as desired. Accordingly, theinvention is not to be restricted, but rather to be given the full scopeof the attached claims and their equivalents.

1. A method for testing the function of a vagal nerve of a patient, themethod comprising: positioning an energy delivery device within theesophagus adjacent a vagal nerve, the vagal nerve being located outsidethe esophagus wall; delivering a high level energy from the energydelivery device sufficient to disrupt the function of the vagal nerve;delivering a lower level of energy from the energy delivery device toanother portion of the vagal nerve; determining whether the function ofthe vagal nerve has been disrupted by measuring the pressure in thestomach after delivering the lower level energy to the vagal nerve. 2.The method of claim 1 further comprising; delivering the lower levelenergy from the energy delivery device to a different portion of thevagal nerve than that to which the high level energy was delivered. 3.The method of claim 2 further comprising determining whether thefunction of the vagal nerve is completely disrupted.
 4. The method ofclaim 1 further comprising measuring the pressure in the stomach beforedelivering the lower level energy to the vagal nerve; and comparing thepressure in the stomach before delivery of the lower level energy to thepressure in the stomach after delivery of the lower level energy.
 5. Themethod of claim 4 wherein the determining step includes comparing thepressure in the stomach before delivery of the lower level energy to thepressure in the stomach after delivery of the lower level energy.
 6. Amethod for testing the function of a vagal nerve comprising: applying anelectrical stimulus to the vagal nerve after delivery of the energysufficient to disrupt the function of the vagal nerve; and measuring thepressure in the stomach after applying the electrical stimulus to thenerve.
 7. The method of claim 6 further comprising: measuring thepressure in the stomach before applying the electrical stimulus to thevagal nerve; and comparing the pressure in the stomach before applyingthe electrical stimulus to the vagal nerve to the pressure in thestomach after applying the electrical stimulus to the vagal nerve. 8.The method of claim 4 further comprising determining that the functionof the vagal nerve is completely disrupted if the pressure in thestomach does not change.
 9. The method of claim 6 further comprisingdetermining that the function of the vagal nerve is completely disruptedif the pressure in the stomach before applying the electrical stimulusto the vagal nerve is substantially the same as the pressure in thestomach after applying the electrical stimulus to the vagal nerve. 10.The method of claim 1 wherein the step of determining whether thefunction of the vagal nerve is disrupted includes measuring a gastricmucosal pH of the stomach.
 11. The method of claim 10 wherein the stepof determining whether the function of the vagal nerve is disruptedincludes introducing PCP-GABA before measuring the gastric mucosal pH ofthe stomach.
 12. The method of claim 2 wherein said different locationis obtained by retracting the energy delivery device further away fromthe stomach.
 13. The method of claim 1 wherein the energy is ultrasound.14. The method of claim 1 wherein the energy sufficient to disrupt thefunction of the vagal nerve is high intensity ultrasound.
 15. The methodof claim 1 wherein the energy sufficient to disrupt the function of thevagal nerve is high intensity focused ultrasound.
 16. The method ofclaim 1 wherein the energy is radio frequency energy.
 17. The method ofclaim 1 wherein the lower energy level is delivered by electrodes whichare passed through the wall of the esophagus.
 18. The method of claim 1further comprising using electrodes to locate a vagal nerve branch. 19.The method of claim 1 wherein the energy delivery device is introducedinto the esophagus through the mouth.
 20. The method of claim 1 whereinthe energy delivery device is delivered to the esophagus through thenose.
 21. The method of claim 1 wherein the lower energy level fallswithin the range of 500 mW/cm2 and 5 W/cm2.
 22. The method of claim 1wherein the high energy level falls within the range of 300 and 3000W/cm2.
 23. The method of claim 21 wherein the high energy level fallswithin the range of 300 and 3000 W/cm2.
 24. The method of claim 1further comprising measuring the pancreatic polypeptide response to asham feeding or a pharmacological stimulation.
 25. The method of claim 1further comprising using the Burge test to apply an electrical voltageto the vagal nerve and determining whether gastric pressure in thestomach changes in response to the electrical voltage.
 26. The method ofclaim 1 further comprising using the Burge test with an inflatableballoon and measuring a distension of the stomach.
 27. The method ofclaim 1 further comprising introducing histamine into the patient andchecking the pH of the mucosa of the stomach.
 28. The method of claim 1further comprising introducing PCP-GABA into the patient.
 29. The methodof claim 1 further comprising introducing insulin into the patient. 30.The method of claim 1 further comprising introducing 2-deoxy-glucoseinto the patient.
 31. The method of claim 1 further comprisingintroducing a neurotransmitter amino acid into the patient.
 32. Themethod of claim 1 further comprising obtaining the pressure in thestomach before delivering the higher level energy to the vagal nerve;delivering the high level energy from the energy delivery devicesufficient to disrupt the function of the vagal nerve at a time afterobtaining the pressure; measuring the pressure in the stomach beforedelivering the lower level energy to the vagal nerve; and comparing thepressure in the stomach before delivery of the lower level energy to thepressure in the stomach after delivery of the lower level energy.